This project is aimed at understanding the chemistry, anatomy and physiology of the fibrous proteins of the brain in health and in disease. We will focus on the comparison of the neurofilaments, glial filaments, microfilaments and microtubules of the brain and of neuronal cells in culture. The relationship of brain intermediate filaments to the 100A-filaments of other cells and tissues will be investigated. Biochemical and immunohistological techniques will be used to localize these proteins during development in clonal cell lines. The proteins of the post-synapic density will be characterized using biochemical and immunological methods and the development of these junctions sill be studied in the mouse retina where there is a temporal separation in the formation of conventional and ribbon synapses. Finally, we shall continue our efforts to purify and characterize the twisted tubules in Alzheimer's Disease.